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(Hypertension. 1999;34:643-648.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Congenic Substitution Mapping Excludes Sa as a Candidate Gene Locus for a Blood Pressure Quantitative Trait Locus on Rat Chromosome 1

Norbert Hübner; Young-Ae Lee; Klaus Lindpaintner; Detlev Ganten; Reinhold Kreutz

From the Max-Delbrück-Center for Molecular Medicine (N.H., Y-A.L., K.L., D.G.), and the Department of Clinical Pharmacology (N.H., D.G., R.K.) and Department of Medicine IV (R.K.), Benjamin Franklin Medical Center, Freie Universität Berlin, Berlin, Germany; the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School (K.L.), Boston, Mass; and the Pharmaceuticals Division of F. Hoffmann-La Roche (K.L.), Basel, Switzerland.

Correspondence to Dr Reinhold Kreutz, Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail Kreutz{at}medizin.fu-berlin.de

Abstract—Previously, linkage analysis in several experimental crosses between hypertensive rat strains and their contrasting reference strains have identified a major quantitative trait locus (QTL) for blood pressure on rat chromosome 1 (Chr 1) spanning the Sa gene locus. In this study, we report the further dissection of this Chr 1 blood pressure QTL with congenic substitution mapping. To address whether the Sa gene represents a candidate gene for the Chr 1 blood pressure QTL, congenic strains were developed by introgressing high blood pressure QTL alleles from the stroke-prone spontaneously hypertensive rat (SHRSP) into the normotensive Wistar-Kyoto (WKY-1) reference strain. Congenic animals carrying a chromosomal segment from stroke-prone spontaneously hypertensive rats between genetic markers Mt1pa and D1Rat200 (including the Sa gene locus) show a significant increase in basal systolic and diastolic blood pressure compared with their normotensive Wistar-Kyoto progenitors (P<0.001, respectively), whereas congenic animals carrying a subfragment of this Chr 1 region defined by markers Mt1pa and D1Rat57 (also spanning the Sa gene) do not show elevated basal blood pressure levels (P=0.83 and P=0.9, respectively). Similar results were obtained for NaCl-induced blood pressure values. Thus, the blood pressure QTL on Chr 1 is located centromeric to the Sa gene locus in a region that is syntenic to human chromosome 11p15.4-p15.3. This region excludes the Sa as a blood pressure–elevating candidate gene locus on the basis of congenic substitution mapping approaches.

Key Words: hypertension, essential • rats, inbred SHR • rats, inbred WKY • genetics • complex traits • crosses, genetic

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